The role of secretory mucosal antibodies in the development and maintenance of protection against Haemophilus influenzae, type b (Hib), a major cause of serious bacterial infections in young children, is poorly understood. Secretory antibodies against viruses and other bacteria have been shown to be present in human mucosal secretions, and to play a protective role against infection with these agents. The mechanisms of the protective function of secretory antibodies against bacterial agents are also not completely understood. The purpose of this proposal is to define the prevalence of secretory antibodies directed against the polyribitol phosphate (PRP) capsular polysaccharide of Hib and the pilus protein of Hib in relation to pharyngeal colonization, and to explore the function of these secretory anti-Hib antibodies. In this project, enzyme immunoassay techniques will be established to quantitate IgG and IgA antibodies directed against two Hib antigens, the capsular polysaccharide (PRP) and the pilus protein. Using these assays, the levels of IgA and IgG anti-PRP and anti-pilus antibodies in the serum and salivary secretions will be compared among asymptomatic nasopharyngeal carriers and patients with invasive Hib disease. In addition, age will be correlated with level and duration of anti-PRP and anti-pilus secretory antibodies. The function of immune secretions in inhibiting Hib attachment to epithelial cells will be investigated in a quantitative in vitro adherence assay using a piliated strain of Hib. A parental vaccine composed of the capsular polysaccharide (PRP) of H. influenzae, type b, has been shown to be ineffective in stimulating young children who are at greatest risk of developing invasive disease. Demonstration of protective mucosal antibodies specific for Hib in the secretions of patients and asymptomatic carriers of Hib may be important in considering various immunologic approaches to the prevention of Hib disease.
